Synaptic Scaling and the Development of a Motor Network

Abstract

Neurons respond homeostatically to chronic changes in network activity with compensatory changes such as a uniform alteration in the size of miniature postsynaptic current (mPSC) amplitudes termed synaptic scaling. However, little is known about the impact of synaptic scaling on the function of neural networks in vivo. We used the embryonic zebrafish to address the effect of synaptic scaling on the neural network underlying locomotion. Activity was decreased during development by TTX injection to block action potentials or CNQX injection to block glutamatergic transmission. Alternatively TNF␣ was chronically applied. Recordings from spinal neurons showed that glutamatergic mPSCs scaled up ϳ25% after activity reduction and fortuitously scaled down ϳ20% after TNF␣ treatment, and were unchanged following blockade of neuromuscular activity alone with ␣-bungarotoxin. Regardless of the direction of scaling, immediately following reversal of treatment no chronic effect was distinguishable in motoneuron activity patterns or in swimming behavior. We also acutely induced a similar increase of glutamatergic mPSC amplitudes using cyclothiazide to reduce AMPA receptor desensitization or decrease of glutamatergic mPSC amplitudes using a low concentration of CNQX to partially block AMPA receptors. Though the strength of the motor output was altered, neither chronic nor acute treatments disrupted the patterning of synaptic activity or swimming. Our results show, for the first time, that scaling of glutamatergic synapses can be induced in vivo in the zebrafish and that synaptic patterning is less plastic than synaptic strength during development.

β-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity

“…Under chronic suppression of neuronal activity, HSP is expressed via an increase in synaptic expression of AMPARs producing an up-scaling of AMPAR-mediated miniature post-synaptic currents (mEPSCs). While most studies show inactivity-induced synaptic scaling in cultured neurons [2, 46, 50, 55], HSP is also observed in vivo including in the spinal cord [16, 19, 33, 59] and in the visual cortex [11, 17, 31, 34, 38]. AMPARs are heterotetrameric ion channels consisting of different compositions of the four subunits GluA1–4, and the most common of which are GluA1/GluA2 and GluA2/GluA3 combinations [5, 13].…”

Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function

“…1B). Synaptic scaling has now been shown in a variety of central neurons both in vitro and in vivo, including neocortical and hippocampal pyramidal neurons and spinal neurons (O'Brien et al 1998;Turrigiano et al 1998;Desai et al 2002;Stellwagen and Malenka 2006;Goel and Lee 2007;Kim and Tsien 2008;Knogler et al 2010). Currently, most of the mechanistic work on synaptic scaling has involved neocortical or hippocampal pyramidal neurons in dissociated culture; whether the mechanisms that underlie synaptic scaling in vivo and in other brain regions are similar or distinct to those for cultured cortical neurons remains an open question.…”

“…For example, during embryonic and early postnatal development, homeostatic mechanisms can ensure that spontaneous activity is present in developing spinal circuits (Gonzalez-Islas and Wenner 2006; Knogler et al 2010), where such activity is vital for driving proper circuit connectivity (Hanson and Landmesser 2004). Similarly, in visual cortex during the second and third postnatal weeks when synaptogenesis is high, there is an inverse relationship between the frequency and amplitude of mEPSCs onto pyramidal neurons, and this can be prevented by raising animals in the dark (Desai et al 2002).…”

Control of lung ventilation following overwintering conditions in bullfrogs,Lithobates catesbeianus

“…From the neural perspective, a wealth of information exists regarding how neurons and circuits maintain target levels of activity despite removing or enhancing activity inputs (termed homeostatic plasticity). However, models to study these processes use pharmacological or pathological paradigms to manipulate neuronal activity in vivo and in vitro primarily at early developmental stages (Hengen et al, 2013;Knogler et al, 2010;Ngodup et al, 2015;Schacher and Hu, 2014;Turrigiano, 2012;Wilhelm and Wenner, 2008). Thus, the bullfrog respiratory control system following overwintering offers a powerful ability to uncover mechanisms leading to and resulting in the preservation (respiratory motor output and hypoxia sensitivity) and deterioration (CO 2 sensitivity) of sensorimotor function in the same species, individual and neural control system after ecologically relevant inactivity.…”